Diabetes is a major health care problem that has reached crisis proportions. The disease accounts for >14% of total national health care expenditures in the US, untold losses of precious human resources, and new therapies are urgently needed. We are developing a glucose sensor with telemetry for long-term (> 1 year) implantation in subcutaneous tissues. In type 1 diabetes, the sensor would help avoid hyperglycemia, warn of hypoglycemia, direct insulin dosing, and provide the missing component of the artificial pancreas. In type 2 diabetes, the sensor would be useful for medication adjustment and reducing mean blood glucose. Blood glucose monitoring is central to all therapies for diabetes. Present monitoring methods rely on sampling by "fingerstick" or recently introduced, short-term percutaneous needle-like senors. These methods are objectionable to most people with diabetes and are not suitable for children. Development by our group of a long-term implantable glucose sensor has been underway for many years. The unique and innovative sensor design based on differential glucose and oxygen detection overcomes limitations of sensor encapsulation by the body. Sensors implanted over 5 months in pigs remain responsive to glucose, although affected by the foreign body response. The sensor and telemetry implant system can serve as a unique experimental tool for the study of mass transfer in tissue surrounding implants, while determing the ability of the system to detect hypoglycemia. Multiple sensor-telemetry units will be implanted in non-diabetic and diabetic pigs for one year and glucose challenges will be performed. Tissue samples will be collected via biopsy for histologic analyses. Blood glucose recordings will be compared quantitatively with standard glucose assay. Mass transfer models will be constructed and predicted substrate fluxes will be compared with actual fluxes measured over the long term by implanted sensors. [unreadable] [unreadable] [unreadable]